Inetetamab combined with tegafur as second-line treatment for human epidermal growth factor receptor-2-positive gastric cancer: A case report

BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes

BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis.Our previous study found that milk fat globule epidermal growth factor 8(MFG-E8)alleviates acinar cell damage during SAP via binding toαvβ3/5 integrins.MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy.AIM To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux.METHODS SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50μg/kg cerulein plus lipopolysaccharide.mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAPinduced liver injury.Cilengitide,a specificαvβ3/5 integrin inhibitor,was used to investigate the possible mechanism of MFG-E8.RESULTS The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice,enhanced autophagy flux in hepatocyte,and worsened the degree of ferroptosis.Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner.Mechanistically,MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells.Cilengitide abolished MFG-E8’s beneficial effects in SAP-induced liver injury.CONCLUSION MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury.MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrinαVβ3/5.

Tyrosine kinase inhibitors and human epidermal growth factor receptor-2 positive breast cancer

The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitors(TKIs)has been of particular interest in the treatment of human malignancies.This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC.

Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer

AIM:To investigate human epidermal growth factor receptor 2(HER2)-phosphatidylinositol 3-kinase(PI3K)-vAkt murine thymoma viral oncogene homolog signaling pathway.METHODS:We analyzed 231 formalin-fixed,paraffinembedded gastric cancer tissue specimens from Japanese patients who had undergone surgical treatment.The patients' age,sex,tumor location,depth of invasion,pathological type,lymph node metastasis,and pathological stage were determined by a review of the medical records.Expression of HER2 was analyzed by immunohistochemistry(IHC) using the HercepTest TM kit.Standard criteria for HER2 positivity(0,1+,2+,and 3+) were used.Tumors that scored 3+ were considered HER2-positive.Expression of phospho Akt(pAkt) was also analyzed by IHC.Tumors were considered pAkt-positive when the percentage of positive tumor cells was 10% or more.PI3K,catalytic,alpha polypeptide(PIK3CA) mutations in exons 1,9 and 20 were analyzed by pyrosequencing.Epstein-Barr virus(EBV) infection was analyzed by in situ hybridization targeting EBV-encoded small RNA(EBER) with an EBER-RNA probe.Microsatellite instability(MSI) was analyzed by polymerase chain reaction using the mononucleotide markers BAT25 and BAT26.RESULTS:HER2 expression levels of 0,1+,2+ and 3+ were found in 167(72%),32(14%),12(5%) and 20(8.7%) samples,respectively.HER2 overexpression(IHC 3+) significantly correlated with intestinal histological type(15/20 vs 98 /205,P = 0.05).PIK3CA mutations were present in 20 cases(8.7%) and significantly correlated with MSI(10/20 vs 9/211,P < 0.01).The mutation frequency was high(21%) in T4 cancers and very low(6%) in T2 cancers.Mutations in exons 1,9 and 20 were detected in 5(2%),9(4%) and 7(3%) cases,respectively.Two new types of PIK3CA mutation,R88Q and R108H,were found in exon1.All PIK3CA mutations were heterozygous missense singlebase substitutions,the most common being H1047R(6/20,30%) in exon20.Eighteen cancers(8%) were EBV-positive and this positivity significantly correlated with a diffuse histological type(13/18 vs 93/198,P = 0.04).There were 7 cases of lymphoepithelioma-like carcinomas(LELC) and 6 of those cases were EBV-positive(percent/EBV:6/18,33%;percent/all LELC:6/7,86%).pAkt expression was positive in 119(53%) cases but showed no correlation with clinicopathological characteristics.pAkt expression was significantly correlated with HER2 overexpression(16/20 vs 103/211,P < 0.01) but not with PIK3CA mutations(12/20 vs 107/211,P = 0.37) or EBV infection(8/18 vs 103/211,P = 0.69).The frequency of pAkt expression was higher in cancers with exon20 mutations(100%) than in those with exon1(40%) or exon9(56%) mutations.One case showed both HER2 overexpression and EBV infection and 3 cases showed both PIK3CA mutations and EBV infection.However,no cases showed both PIK3CA mutations and HER2 overexpression.One EBVpositive cancer with PIK3CA mutation(H1047R) was MSI-positive.Three of these 4 cases were positive for pAkt expression.In survival analysis,pAkt expression significantly correlated with a poor prognosis(hazard ratio 1.75;95%CI:1.12-2.80,P = 0.02).CONCLUSION:HER2 expression,PIK3CA mutations and EBV infection in gastric cancer were characterized.pAkt expression significantly correlates with HER2 expression and with a poor prognosis.

High levels of serum platelet-derived growth factor-AA and human epidermal growth factor receptor-2 are predictors of colorectal cancer liver metastasis

AIM To develop predictive markers in blood for colorectal cancer liver metastasis.METHODS Twenty colorectal cancer patients were selected and divided into two groups. Group A consisted of 10 patients whose pathological TNM stage was ⅢC(T3-4N2M0), while another 10 patients with synchronous liver metastasis(TNM stage Ⅳ) were recruited for group B. During the surgical procedure, a 10-ml drainage vein(DV) blood sample was obtained from the DV of the tumor-bearing segment prior to the ligation of the DV. At the same time, a 10-ml peripheral vein(PV) blood sample was collected via peripheral venipuncture. The serum levels of 24 molecules that are potentially involved in the mechanism of liver metastasis in both DV blood and PV blood were analyzed by using high-throughput enzyme-linked immunosorbent assay technology.RESULTS Univariate analysis revealed that platelet-derivedgrowth factor AA(PDGFAA) in DV blood(d PDGFAA)(P = 0.001), PDGFAA in PV blood(p PDGFAA)(P = 0.007), and human epidermal growth factor receptor-2 in PV blood(p HER2)(P = 0.001), p MMP7(P = 0.028), pR ANTES(P = 0.013), and pE GF(P = 0.007) were significantly correlated with synchronous liver metastasis. Multivariate analysis identified d PDGFAA(HR = 1.001, P = 0.033) and p HER2(HR = 1.003, P = 0.019) as independent predictive factors for synchronous liver metastasis. Besides, high peripheral HER2 level may also be a risk factor for metachronous liver metastasis, although the difference did not reach statistical significance(P = 0.06). Significant correlations were found between paired DV and PV blood levels for PDGFAA(r = 0.794, P < 0.001), but not for HER2(r = 0.189, P = 0.424).CONCLUSION PDGFAA in tumor drainage and HER2 in PV blood may be useful predictive factors for synchronous liver metastasis of colorectal cancer.

Human epidermal growth factor receptor-2 gene amplification in gastric cancer using tissue microarray technology

AIM:To assess human epidermal growth factor receptor-2 (HER2)-status in gastric cancer and matched lymph node metastases by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH).METHODS:120 cases of primary gastric carcinomas and 45 matched lymph node metastases from patients with full clinicopathological features were mounted onto multiple-punch and single-punch tissue microarrays,respectively,and examined for HER2 overexpression and gene amplification by IHC and CISH.RESULTS:Twenty-four tumors (20%) expressed HER2 immunohistochemically.An IHC score of ≥ 2+ was observed in 20 tumors (16.6%).HER2 amplification was detected by CISH in 19 tumors (15.8%) and in their matched lymph node metastases.A high concordancerate was found between HER2 positivity (as detected by IHC) and HER2 gene amplification (as detected by CISH),since 19 of the 20 IHC positive cases were amplified (95%).All amplified cases had 2+ or 3+ IHC results.Amplification was associated with intestinal phenotype (P < 0.05).No association with grading,staging or survival was found.CONCLUSION:In gastric cancer,HER2 amplification is the main mechanism for HER2 protein overexpression and is preserved in lymph node metastases.

Activation of Rac1-PI3K/Akt is required for epidermal growth factorinduced PAK1 activation and cell migration in MDA-MB-231 breast cancer cells

Epidermal growth factor （EGF） may increase cell motility, an event implicated in cancer cell invasion and metastasis. However, the underlying mechanisms for EGF-induced cell motility remain elusive. In this study, we found that EGF treatment could activate Ras-related C3 botulinum toxin substrate 1 （Racl）, PI3K/Akt and p21- actived kinase （PAK1） along with cell migration. Ectopic expression of PAK1 K299R, a dominant negative PAK1 mutant, could largely abolish EGF-induced cell migration. Blocking PI3K/Akt signalling with LY294002 or Akt siRNA remarkably inhibited both EGF-induced PAK1 activation and cell migration. Furthermore, expression of dominant-negative Racl （T17N） could largely block EGF-induced PI3K/Akt-PAK1 activation and cell migration. Interestingly, EGF could induce a significant production of ROS, and N-acetyl-L-cysteine, a scavenger of ROS which abolished the EGF-induced ROS generation, cell migration, as well as activation of PI3K/Akt and PAK, but not Racl. Our study demonstrated that EGF-induced cell migration involves a cascade of signalling events, including activation of Racl, generation of ROS and subsequent activation of PI3K/Akt and PAK1.

PI3K-mediated glioprotective effect of epidermal growth factor under oxidative stress conditions

AIM:To determine the effects of epidermal growth factor(EGF)on the proliferation and migration of Müller cell line Moorfields/Institute of Ophthalmology-Müller 1(MIO-M1),and its related molecular mechanisms under normal and oxidative stress conditions.METHODS:Müller cells were cultured with different concentrations of EGF in the presence or absence of varied amounts of H2O2and glucose oxidase(GO)which induced oxidative stress.The proliferation and migration of Müller cells were examined by 5-Bromo-2-deoxy Uridine(BrdU),MTT assay,Transwell assay and scratch wound healing assays.The cell viability was determined with the MTT assay.The secretion of EGF by Müller cells was evaluated by ELISA.Western blot was performed to detect the activation of extracellular regulated protein kinases(ERK)1/2 and Akt signal pathways.RESULTS:EGF stimulated the proliferation and migration of Müller cells in a concentration-dependent manner in vitro.Under oxidative damage condition,2h of pretreatment with 10-100 ng/mL EGF can mostly inhibit 50% lethal dose of 0.08 mmol/L H2O2-induced cell damage.The Western blot results showed that after Müller cells were exposed to varying EGF for 24h,Akt and ERK1/2 were phosphorylated in a dose-dependent manner.In the presence of the LY294002,the potent PI3K inhibitor,the p-Akt was significantly attenuated.CONCLUSION:EGF may induce the proliferation and migration of human Müller cells through the Akt and the ERK1/2 signal pathways,and induce PI3K-mediated glioprotective effect under oxidative stress.

Mechanisms of resistance to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer

The prognosis of patients with metastatic colorectal cancer (mCRC) remain poor despite the impressive improvement of treatments observed over the last 20 years that led to an increase in median overall survival from 6 mo, with the only best supportive care, to approximately 30 mo with the introduction of active chemotherapy drugs and targeted agents. The monoclonal antibodies (moAbs) cetuximab and panitumumab, directed against the epidermal growth factor receptor (EGFR), undoubtedly represent a major step forward in the treatment of mCRC, given the relevant efficacy in terms of progression-free survival, overall survival, response rate, and quality of life observed in several phase III clinical trials among different lines of treatment. However, the anti-EGFR moAbs were shown only to be effective in a subset of patients. For instance, KRAS and NRAS mutations have been identified as biomarkers of resistance to these drugs, improving the selection of patients who might derive a benefit from these treatments. Nevertheless, several other alterations might affect the response to these drugs, and unfortunately, even the responders eventually become resistant by developing secondary (or acquired) resistance in approximately 13-18 mo. Several studies highlighted that the landscape of responsible alterations of both primary and acquired resistance to anti-EGFR drugs biochemically converge into MEK-ERK and PIK3CA-AKT pathways. In this review, we describe the currently known mechanisms of primary and acquired resistance to anti-EGFR moAbs together with the various strategies evaluated to prevent, overcame or revert them.

Increased expressions of vascular endothelial growth factor(VEGF),VEGF-C and VEGF receptor-3 in prostate cancer tissue are associated with tumor progression

Aim： To investigate the differences in microvessel densities （MVD） and the expressions of vascular endothelial growth factor （VEGF）, VEGF-C and VEGF receptor-3 （VEGFR-3） between prostate cancer （PCa） tissues and adjacent benign tissues, and to explore the correlations among MVD, Jewett-Whitmore staging, Gleason scores and expressions of VEGF, VEGF-C and VEGFR-3 in the progression of PCa. Methods： An immunohistochemical approach was adopted to detect the expressions of CD34, VEGF, VEGF-C and VEGFR-3 in both cancer areas and peripheral benign areas of 71 primary prostatic adenocarcinoma specimens. A statistic analysis was then performed according to the experimental and clinic data. Results： Significantly upregulated expressions of VEGF, VEGF-C and VEGFR-3 were all found in malignant epithelium/cancer cells compared with adjacent benign epithelium （P 〈 0.01）. Patients in stage D had a significantly higher score than patients in stage A, B or C when comparing the expression of VEGF-C or VEGFR-3 in the tumor area （P 〈 0.01）. In addition, significant correlations were observed between Jewett-Whitmore staging and VEGF-C （rs = 0.738, P 〈 0.01）, clinical staging and VEGFR-3 （rs = 0.410, P 〈 0.01）, VEGF-C and Gleason scores （rs = 0.401, P 〈 0.01）, VEGFR-3 and Gleason scores （rs = 0.581, P 〈 0.001） and MVD and VEGF （rs = 0.492, P 〈 0.001）. Conclusion： Increased expressions of VEGF and VEGF-C were closely associ- ated with progression of PCa. The main contribution of increased VEGF expression for PCa progression was to upregulate MVD, which maintained the growth advantage of tumor tissue. However, the chief role of increased expressions of VEGF-C and VEGFR-3 was to enhance lymphangiogenesis and provide a main pathway for cancer cells to disseminate. （Asian J Androl 2006 Mar; 8： 169-175）

Repurposed anti-cancer epidermal growth factor receptor inhibitors: mechanisms of neuroprotective effects in Alzheimer’s disease

Numerous molecular mechanisms are being examined in an attempt to discover disease-modifying drugs to slow down the underlying neurodegeneration in Alzheimer’s disease.Recent studies have shown the beneficial effects of epidermal growth factor receptor inhibitors on the enhancement of behavioral and pathological sequelae in Alzheimer’s disease.Despite the promising effects of epidermal growth factor receptor inhibitors in Alzheimer’s disease,there is no irrefutable neuroprotective evidence in well-established animal models using epidermal growth factor receptor inhibitors due to many un-explored downstream signaling pathways.This caused controversy about the potential involvement of epidermal growth factor receptor inhibitors in any prospective clinical trial.In this review,the mystery beyond the under-investigation of epidermal growth factor receptor in Alzheimer’s disease will be discussed.Furthermore,their molecular mechanisms in neurodegeneration will be explained.Also,we will shed light on SARS-COVID-19 induced neurological manifestations mediated by epidermal growth factor modulation.Finally,we will discuss future perspectives and under-examined epidermal growth factor receptor downstream signaling pathways that warrant more exploration.We conclude that epidermal growth factor receptor inhibitors are novel effective therapeutic approaches that require further research in attempts to be repositioned in the delay of Alzheimer’s disease progression.

NRG1、HER3在前列腺癌组织中的表达及其与临床病理特征和预后的关系

目的研究前列腺癌(PC)组织中神经调节蛋白1(NRG1)、人表皮生长因子受体3(HER3)表达与临床病理特征及预后的关系。方法选取2015年2月—2020年2月吉林省人民医院泌尿外科诊治PC患者96例,免疫组织化学检测组织中NRG1、HER3表达;Kaplan-Meier曲线(Log-Rank检验)比较不同NRG1、HER3表达对PC患者预后的影响;COX回归分析PC患者预后的影响因素。结果PC癌组织中NRG1、HER3阳性率分别为78.13%(75/96)、75.00%(72/96),高于癌旁组织6.25%(6/96)、8.33%(8/96)(χ^(2)/P=101.670/<0.001,87.771/<0.001)。TNM分期Ⅲ期、Gleason评分>7分及术前PSA水平≥20μg/L患者癌组织中NRG1、HER3阳性率大于TNM分期Ⅰ~Ⅱ期、Gleason评分≤7分及术前PSA水平<20μg/L(χ^(2)/P=6.181/0.013,8.533/0.003;7.731/0.005,6.769/0.009;6.508/0.011,7.376/0.007)。NRG1阳性组、HER3阳性组3年累积无进展生存率分别低于NRG1阴性组、HER3阴性组(χ^(2)/P=4.267/0.039,5.499/0.019)。TNM分期Ⅲ期、Gleason评分>7分、术前PSA≥20μg/L、NRG1阳性,HER3阳性是影响PC患者预后的独立危险因素[OR(95%CI)=1.448(1.118~1.875),1.401(1.138~1.724),1.353(1.059~1.728),1.338(1.057~1.692),1.293(1.014~1.649)]。结论PC癌组织中NRG1、HER3表达升高,与PC不良临床病理特征相关,是新的评估PC预后的肿瘤标志物。

PIK3CA突变与乳腺癌临床病理特征及预后的相关性

目的探讨乳腺癌标本中磷脂酰肌醇激酶-3-催化亚基α(PIK3CA)突变与侵袭性乳腺癌临床病理特征及预后的相关性。方法收集2018年1月至2020年1月确诊为乳腺癌的181例患者临床病理资料,用免疫组织化学(IHC)法检测乳腺癌雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER2)、Ki-67等指标,RT-qPCR检测乳腺癌中PIK3CA外显子9(exon9)和外显子20(exon20)的突变。结果181例侵袭性乳腺癌中PIK3CA突变70例,其中31例(44.28%)exon9突变、39例(55.71%)exon20突变。PIK3CA突变与乳腺癌分子分型有明显差异(P<0.05)。PIK3CA突变与乳腺癌的Ki67表达有明显差异(P<0.05)。34例(48.57%)HR+/HER2-组PIK3CA突变,36例(51.43%)非HR+/HER2-组突变,二者PIK3CA突变分布有明显差异(P<0.05)。PIK3CA突变患者病死率高于PIK3CA野生型(P<0.05)。结论PIK3CA突变与乳腺癌分子分型、Ki67增值指数及预后相关,可为患者精准治疗提供参考。

食管鳞癌组织中EGFR、KRAS及PIK3CA基因突变的检测及其临床意义分析

目的分析食管鳞癌组织中表皮生长因子受体(EGFR)、Kirsten鼠类肉瘤病毒癌基因(KRAS)和磷脂酰肌醇3激酶(PIK3CA)基因的突变情况及其与患者临床特征的关系。方法选取2006年1月至2012年12月在新疆医科大学第一附属医院确诊的210例食管鳞癌患者的组织标本进行DNA提取和目标位点扩增,再利用一代测序的方法对EGFR18号和21号外显子、KRAS2号外显子、PIK3CA9号外显子进行测序,探讨各基因突变情况及其与临床病理特征的关系,并分析不同基因突变之间的相关性。结果210例食管鳞癌标本中EGFR基因突变率为27.14%,KRAS基因突变率为14.29%,PIK3CA基因突变率为18.59%,EGFR和KRAS双基因联合突变率为4.76%,EGFR和PIK3CA双基因联合突变率为5.71%,EGFR、KRAS、PIK3CA三基因联合突变率为1.43%。EGFR基因突变与性别、肿瘤直径、分化程度具有相关性(P<0.05),KRAS基因突变与肿瘤直径、分化程度、T分期、临床分期具有相关性(P<0.05),PIK3CA基因突变与性别、肿瘤直径、分化程度具有相关性(P<0.05),EGFR和PIK3CA联合突变与性别、肿瘤直径、分化程度具有相关性(P<0.05)。EGFR基因突变与KRAS基因突变具有相关性(P<0.05),而EGFR基因突变与PIK3CA基因突变之间无相关性(P>0.05)。结论食管鳞癌组织中EGFR基因突变率最高,PIK3CA基因突变率次之,KRAS基因突变率最低;EGFR与KRAS或PIK3CA基因突变联合检测具有一定的临床意义。

非小细胞肺癌组织AIP1、EDIL3表达变化观察

目的观察非小细胞肺癌(NSCLC)组织凋亡信号调节激酶1-相互作用蛋白1(AIP1)、表皮生长因子样结构域3(EDIL3)表达变化,分析其与微血管密度(MVD)、临床病理特征及预后的关系,为NSCLC的靶向治疗提供新的干预靶点。方法纳入155例NSCLC患者,免疫组织化学法检测癌组织和癌旁组织中AIP1、EDIL3蛋白,Weidner法检测癌组织MVD。比较不同AIP1、EDIL3表达的NSCLC患者MVD值及不同临床病理特征NSCLC患者癌组织AIP1、EDIL3表达水平。Kaplan-Meier生存曲线分析不同AIP1、EDIL3表达的NSCLC患者生存情况,多因素Cox回归分析NSCLC患者预后的影响因素。结果与癌旁组织比较,NSCLC癌组织中EDIL3阳性表达率高、AIP1阳性表达率低(P均<0.05)。不同分化程度、淋巴结转移、肿瘤直径、TNM分期的NSCLC患者癌组织中AIP1、EDIL3蛋白阳性表达率比较,P均<0.05。AIP1阳性表达的NSCLC患者癌组织MVD值低于AIP1阴性表达者(P<0.05),EDIL3阳性表达的NSCLC患者癌组织MVD值高于EDIL3阴性表达者(P<0.05)。EDIL3阳性表达的NSCLC患者3年总生存(OS)率低于EDIL3阴性表达者(P<0.05),AIP1阳性表达的NSCLC患者3年OS率高于AIP1阴性表达者(P<0.05)。淋巴结转移、TNM分期ⅢA期、EDIL3阳性表达是NSCLC患者预后不良的危险因素(P均<0.05),AIP1阳性表达是保护因素(P<0.05)。结论NSCLC癌组织中AIP1阳性表达率降低,EDIL3阳性表达率升高;癌组织中AIP1、EDIL3阳性表达率与MVD、分化程度、淋巴结转移、肿瘤直径、TNM分期有关,是NSCLC预后不良的影响因素。

Flt3L、TGF-β1及EGFR与急性髓系白血病患者不良预后的关系

目的探究FMS样酪氨酸激酶3配体(Flt3L)、转化生长因子β1(TGF-β1)及表皮生长因子受体(EGFR)与急性髓系白血病(AML)患者不良预后的关系。方法选取120例首次确诊AML患者作为观察组,募集同期体检的100例健康志愿者为对照组,比较2组的Flt3L、TGF-β1及EGFR水平。观察组患者出院后随访3~12个月,根据预后情况将患者分为良好组(86例)和不良组(34例),比较2组的临床资料,采用COX模型分析上述指标与患者不良预后的关系,采用受试者工作特征(ROC)曲线探究上述指标对AML患者不良预后的预测效能。结果观察组Flt3L、TGF-β1水平低于对照组,EGFR水平高于对照组,差异有统计学意义(P<0.05)。不同预后AML患者的Flt3L、TGF-β1及EGFR水平比较差异有统计学意义(P<0.05);COX模型分析显示Flt3L、TGF-β1及EGFR水平为AML患者预后不良的独立影响因素(P<0.05)。经ROC曲线分析显示,Flt3L、TGF-β1及EGFR水平预测AML患者预后不良的AUC为0.874、0.838、0.858。结论Flt3L、TGF-β1及EGFR与AML患者不良预后相关。

Distribution and localization of fibroblast growth factor-8 in rat brain and nerve cells during neural stem/progenitor cell differentiation

The present study explored the distribution and localization of fibroblast growth factor-8 and its potential receptor, fibroblast growth factor receptor-3, in adult rat brain in vivo and in nerve cells during differentiation of neural stem/progenitor cells in vitro. Immunohistochemistry was used to examine the distribution of fibroblast growth factor-8 in adult rat brain in vivo. Localization of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in cells during neural stem/progenitor cell differentiation in vitro was detected by immunofluorescence. Flow cytometry and immunofluorescence were used to evaluate the effect of an anti-fibroblast growth factor-8 antibody on neural stem/progenitor cell differentiation and expansion in vitro. Results from this study confirmed that fibroblast growth factor-8 was mainly distributed in adult midbrain, namely the substantia nigra, compact part, dorsal tier, substantia nigra and reticular part, but was not detected in the forebrain comprising the caudate putamen and striatum. Unusual results were obtained in retrosplenial locations of adult rat brain. We found that fibroblast growth factor-8 and fibroblast growth factor receptor-3 were distributed on the cell membrane and in the cytoplasm of nerve cells using immunohistochemistry and immunofluorescence analyses. We considered that the distribution of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in neural cells corresponded to the characteristics of fibroblast growth factor-8, a secretory factor. Addition of an anti-fibroblast growth factor-8 antibody to cultures significantly affected the rate of expansion and differentiation of neural stem/progenitor cells. In contrast, addition of recombinant fibroblast growth factor-8 to differentiation medium promoted neural stem/progenitor cell differentiation and increased the final yields of dopaminergic neurons and total neurons. Our study may help delineate the important roles of fibroblast growth factor-8 in brain activities and neural stem/progenitor cell differentiation.

Ginkgol C17:1 inhibits tumor growth by blunting the EGF-PI3K/Akt signaling pathway

Ginkgol C17：1 has been shown to inhibit apoptosis and migration of cancer cells,but the underlying mechanisms are not fully elucidated.In this study,we explored whether the inhibitory effects of Ginkgol C17：1 were associated with epidermal growth factor receptor（EGFR） and PI3K/Akt signaling.The results showed that EGF treatment increased the phosphorylation of EGFR,PI3 K,Akt,mTOR and NF-κB,and also enhanced the proliferation,migration and invasion of HepG2 cells.Ginkgol C17：1 dose-dependently inhibited EGF-induced phosphorylation/activation of all the key components including EGFR,PI3 K,Akt,mTOR and NF-kB,leading to a significant reduction either of proliferation or migration and invasion of HepG2 cells.Notably,treatment with Ginkgol C17：1 in mice suppressed the growth of tumor mass in vivo,and expression of EGFR in the tumor tissue.The results suggest that Ginkgol C17：1 is a potent tumor inhibiting compound that acts on EGF-induced signal transduction of the PI3K/Akt signaling pathways,and may represent a clinically interesting candidate for cancer therapy.

ω-3多不饱和脂肪酸改善宠物毛发的应用及机理

ω-3多不饱和脂肪酸是动物体内不能合成但生命活动不可或缺的一类脂肪酸。在宠物健康领域,越来越多的研究发现ω-3多不饱和脂肪酸可用于改善宠物毛发,但相关机制尚未完全明确。文章综述了ω-3多不饱和脂肪酸用于改善宠物犬和兔毛发的相关研究,并梳理了ω-3多不饱和脂肪酸改善毛发的可能机制,旨在为ω-3多不饱和脂肪酸应用于宠物行业改善宠物毛发提供参考。

血清sErbB3、HSP70水平对肝癌患者化疗后预后及生存期的评估价值

目的探讨血清分泌型人类表皮生长因子受体3(sErbB3)、热休克蛋白70(HSP70)水平与原发性肝癌(PLC)患者临床病理特征的关系及对化疗后预后及生存期的评估价值。方法回顾性分析62例PLC患者的临床资料,并将其设置为观察组(n=62);另回顾性分析同期体检的50例健康受试者的临床资料,将其设置为对照组(n=50)。采用酶联免疫吸附法(ELISA)检测2组受试者血清中sErbB3、HSP70水平,分析PLC患者血清中sErbB3、HSP70水平与临床病理特征的关系;绘制ROC曲线评估血清sErbB3、HSP70预测PLC患者预后的价值,Cox回归模型分析PLC患者预后影响因素。结果与健康受试者比较,PLC患者血清中sErbB3、HSP70水平显著升高(P<0.05)。PLC患者血清中sErbB3水平与肿瘤直径、肿瘤数目、TNM分期等相关,HSP70水平与肿瘤直径、肿瘤数目、门静脉癌栓、TNM分期等相关(P<0.05)。sErbB3高水平组化疗后平均生存时间为(28.76±4.72)个月,sErbB3低水平组化疗后平均生存时间为(32.31±3.52)个月,差异有统计学意义(t=3.382,P<0.05)。HSP70高水平组平均生存时间(29.45±4.26)个月,HSP70低水平组化疗后平均生存时间为(31.97±3.74)个月,差异有统计学意义(t=2.479,P<0.05)。ROC结果显示血清中sErbB3、HSP70水平联合检测诊断的灵敏度和特异度分别为80.00%和74.07%;Cox回归模型分析结果显示,肿瘤多发、TNM高分期、sErbB3高水平、HSP70高水平是PLC患者预后的独立危险因素(P<0.05)。结论PLC患者血清中sErbB3和HSP70表达水平显著升高,与临床病理特征密切相关,是PLC患者预后预测的重要指标。